Journal of Biomolecular Structure & Dynamics最新文献

{"title":"G4-interacting ligands: paving the way for precision medicine and molecular diagnostics.","authors":"Patnaik Amit, Sinha Anita, Oraon Vinay, Sahu Duryodhan","doi":"10.1080/07391102.2024.2306498","DOIUrl":"10.1080/07391102.2024.2306498","url":null,"abstract":"<p><p>Amidst the ever-evolving landscape of biomedical research, G-quadruplex (G4) structures have emerged as captivating therapeutic targets, holding immense promise for precision medicine and molecular diagnostics. These intricate DNA or RNA formations play crucial roles in regulating gene expression and are implicated in the pathogenesis of various diseases, including cancer and neurological disorders. The interaction between G4s and ligands derived from medicinal plants offers a compelling avenue for therapeutic intervention and diagnostic applications. G4-interacting ligands have demonstrated remarkable potential as therapeutic agents, selectively targeting G4 structures and modulating their biological functions. However, the effective delivery of these ligands into living cells remains a formidable challenge. Existing physical and biochemical methods are often limited to <i>in vitro</i> settings due to concerns regarding toxicity and nonspecific binding. Overcoming this delivery hurdle is paramount for translating G4-targeting therapies into clinically viable treatments. The development of novel G4 ligands with enhanced affinity and selectivity is essential for realizing the full therapeutic potential of G4-targeting strategies. Understanding the shared structural features of G4 ligands, such as the presence of an aromatic core for π-π stacking interactions and positive moieties for interactions with DNA or RNA backbones, provides valuable insights into ligand design. G4/ligand interactions hold immense promise for molecular diagnostics. By exploiting the specific recognition and binding capabilities of G4 ligands, researchers can develop biosensors and bioimaging tools for the detection and diagnosis of G4-related diseases. These diagnostic tools have the potential to revolutionize disease management by enabling early detection, personalized treatment plans, and improved patient outcomes.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5068-5073"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139542646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating anti-sclerostin mechanism of baicalein using LRP6-Sclersotin complex of canonical Wnt/β-catenin signaling pathway.","authors":"Rajeshwari Muniyasamy, I Manjubala","doi":"10.1080/07391102.2024.2306494","DOIUrl":"10.1080/07391102.2024.2306494","url":null,"abstract":"<p><p>Flavonoids are polyphenolic compounds produced by plants as secondary metabolites that are known to exhibit wide range of pharmaceutical properties. Flavonoids from different medicinal plants have been used in traditional medicine to treat several musculoskeletal disorders for centuries. Of the numerous flavonoids, baicalein from <i>Oroxylum indicum</i> has a well-documented protective effect in skeletal health. However, studies into its influence on the canonical Wnt/β-catenin signaling pathway for musculoskeletal disorders remain limited. With the results of our previous study, the current research investigated the molecular mechanism of baicalein to inhibit the interaction between LRP6 and sclerostin to activate the canonical Wnt/β-catenin signaling pathway. Molecular docking revealed that baicalein docks between LRP6 and sclerostin with a binding energy of -8.4 kcal/mol and interacts with key binding residues of both the proteins. The molecular dynamics simulations predicted the stability of baicalein through 100 ns with more conformational changes observed in sclerostin than LRP6 especially in and around the PNAIG motif of loop-2 region, hinting at a possible inhibitory effect of baicalein over sclerostin. The findings of this research could pave the way for novel drug design approaches while promoting the use of natural flavonoids as potential therapeutics for musculoskeletal disorders.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5009-5019"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139491482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular docking, molecular dynamics, MM/PBSA approaches and bioactivity studies of nepetanudoside B isolated from endemic <i>Nepeta aristata</i>.","authors":"Yunus Başar, İbrahim Demirtaş, Semiha Yenigün, Yaşar İpek, Tevfik Özen, Lütfi Behçet","doi":"10.1080/07391102.2024.2309641","DOIUrl":"10.1080/07391102.2024.2309641","url":null,"abstract":"<p><p>Nepetanudoside B (NNB) was isolated from aerial parts of endemic <i>Nepeta aristata</i> crude extract (CH₃OH-CHCl₃) using silica gel (<i>n</i>-hexane, methanol, ethyl acetate, and dichlorometane, respectively) and sephadex LH-20 (65% Methanol-35% Chloroform) column chromatographies. <i>Preparative</i>-HPLC was used to purify NNB after activity-guided isolation of methanol sub-fractions with enzyme inhibitory and DNA protective properties. The NNB was determined using ¹H,¹³C, COSY, HSQC, HMBC, and LC-MS/MS. The study compared the effects of NNB with conventional drugs in terms of its ability to inhibit enzymes such as urease, α-amylase, carbonic anhydrase (CA), lipase, α-glucosidase, and tyrosinase, as well as its ability to protect DNA. Enzyme kinetic and molecular docking were also used to evaluate this. NNB exhibited the best inhibitory activity on urease (1.28 ± 0.00 µg/mL), lipase (5.83 ± 0.10 µg/mL), BChE (3.73 ± 0.46 µg/mL), tyrosinase (7.39 ± 0.00 µg/mL), α-glucosidase (10.95 ± 0.00 µg/mL), α-amylase (22.11 ± 1.03 µg/mL) and AChE (25.68 ± 3.32 µg/mL), respectively. NNB has higher MolDock scores with binding energy in α-glucosidase (-233) and BChE (-8.90 kcal/mol). In enzyme kinetics studies, it was determined that urease, AChE, α-glucosidase, lipase, and CA were non-competitive , while BChE and tyrosinase were competitive inhibition mechanisms. Their <i>K_i</i> values were calculated as 0.09, 0.24, 0.09, 0.10, 0.08, 0.05, and 0.07 mM, respectively. Molecular dynamics simulation studies were performed for the interactions of NNB-BChE with MM/PBSA binding free energey RMSD, RMSF, Rg, SASA, and also the number of hydrogen bonds was calculated. The suitability and effectiveness of NNB have been proven in the food and pharmaceutical industries. The NNB molecule may lead to development studies as a BChE inhibitor.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5486-5499"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139575842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular dynamics simulation study on the binding mechanism between carbon nanotubes and RNA-dependent RNA polymerase.","authors":"Zhaopeng Ma, Jianqiang Xu, Chenchen Wang, Zhicong Liu, Guanglai Zhu","doi":"10.1080/07391102.2024.2308781","DOIUrl":"10.1080/07391102.2024.2308781","url":null,"abstract":"<p><p>Carbon nanotubes (CNTs) have potential prospects in disease treatment, so it is of great significance to study CNTs as the possible inhibitors of RNA-dependent RNA polymerase (RdRp). Through the way of using the RdRp of SARS-COV-2 as a model, five armchair single-walled carbon nanotubes (SWCNTs) (namely Dn, which stands for CNTs (n, m = n), <i>n</i> = 3-7) and RdRp have been selected to study the interactions by means of molecular docking and molecular dynamics simulation. After five SWCNT-RdRp complex systems have been subjected to the molecular dynamics simulations of 100 ns, and Molecular Mechanics Poisson - Boltzmann Surface Area (MMPBSA) has been used to calculate the binding free energy, it is found that the binding free energy of the D6 system (-189.541 kJ/mol) is significantly higher than that of the other four systems, and most of the amino acids with strong positive effects on binding are usually basic amino acids. What's more, in the further investigation of the specific interaction mechanism between CNT (6,6) and RdRp, it is revealed that the three amino acid residues LYS545, ARG553 and ARG555 located in the nucleoside triphosphate (NTP) entry channel all have strong effects. In addition, it is also observed that when ARG555 has been inserted into SWCNT, a stable structure will be formed, which will break the original NTP entry channel structure and inhibit virus replication. Therefore, it can be concluded that certain specific types of SWCNT, such as CNT (6,6), could be potential small molecule inhibitors in the treatment of coronavirus.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5280-5289"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139540818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In silico</i> and structural investigation of sulfonamides targeting VraSR two component system in methicillin-resistant <i>Staphylococcus aureus</i>.","authors":"Abhishek Kumar Verma, Sandeep Kumar Srivastava","doi":"10.1080/07391102.2024.2309679","DOIUrl":"10.1080/07391102.2024.2309679","url":null,"abstract":"<p><p>Drug-resistant <i>Staphylococcus aureus</i> strains are global health concerns. Several studies have shown that these strains can develop defences against cell wall antibiotics such as β-lactams, glycopeptides and daptomycin which target cell wall biosynthesis. The coordination of these responses have been associated with two component system (TCS) regulated by histidine kinase protein (VraS) and its cognate regulator VraR which influences the target DNA upon signal recognition. Computer-based screening methods, predictions and simulations have emerged as more efficient and quick ways to identify promising new compound leads from large databases against emerging drug targets thus allowing prediction of small select set of molecules for further validations. These combined approaches conserve valuable time and resources. Due to methicillin resistance, sulfonamide-derivative medications have been found to be effective treatment strategy to treat <i>S. aureus</i> infections. The current study used ligand-based virtual screening (LBVS) to identify powerful sulfonamide derivative inhibitors from an antibacterial compound library against VraSR signaling components, VraS and VraR. We identified promising sulfonamide derivative [compound 5: (4-[(1-{[(3,5-Dimethoxyphenyl)Carbamoyl]Methyl}-2,4-Dioxo-1,2,3,4-Tetrahydroquinazolin-3-Yl)Methyl]-N-[(Furan-2-Yl)Methyl]Benzamide)] with reasonable binding parameters of -31.38 kJ/mol and ΔG_bind score of -294.32 kJ/mol against ATP binding domain of sensor kinase VraS. We further identified four compounds N1 (PCID83276726), N3 (PCID83276757), N9 (PCID3672584), and N10 (PCID20900589) against VraR DNA binding domain (VraR_C) with ΔG_bind energies of -190.27, -237.54, -165.21, and -190.88 kJ/mol, respectively. Structural and simulation analyses further suggest their stable interactions with DNA interacting residues and potential to disrupt DNA binding domain dimerization; therefore, it is prudent to further investigate and characterize them as VraR dimer disruptors and inhibit other promoter binding site. Interestingly, the discovery of drugs that target VraS and VraR may open new therapeutic avenues for drug-resistant <i>S. aureus</i>. These predictions based on screening, simulations and binding affinities against VraSR components hold promise for opening novel therapeutic avenues against drug-resistant <i>S. aureus</i> and present opportunities for repositioning efforts. These efforts aim to create analogs with enhanced potency and selectivity against two-component signaling systems that significantly contribute to virulence in MRSA or VRSA. These analyses contribute valuable insights into potential avenues for combating antibiotic-resistant <i>S. aureus</i> through computationally driven drug discovery strategies.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5606-5626"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enzyme engineering of choline oxidase for improving stability.","authors":"Sonia Kaushik, Rashmi Rameshwari, Shilpa S Chapadgaonkar","doi":"10.1080/07391102.2024.2309650","DOIUrl":"10.1080/07391102.2024.2309650","url":null,"abstract":"<p><p>Functioning as a flavoprotein, choline oxidase facilitates the transformation of choline into glycine betaine. Notably, choline oxidase and its resultant product, glycine betaine, find extensive applications across various industries and fields of study. However, its high sensitivity and tendency to lose functional activity at high temperatures reduces its industrial usage. MD simulation and mutation studies have revealed the role of certain residues responsible for the enzyme's thermal instability. This study focuses on inducing thermal stability to choline oxidase of A. <i>globiformis</i> through computational approaches at a maximum temperature of 60 °C. MD simulation analysis showed that Trp 331, Val 464 and Ser 101 contribute to structural instability, leading to the instability at 60 °C. Mutation of these residues with phenylalanine residues and simulation of the mutated enzyme at 60 °C exhibited thermostability and insignificant residual fluctuation. The re-docking and MM/GBSA analyses further validated the mutated enzyme's binding affinity and catalytic activity.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5593-5605"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of potent inhibitors targeting <i>Tribolium castaneum</i> GSTe2 via structure-based screening and molecular dynamics simulation.","authors":"KumChol Kim, Wenjing Zhang, Peng Chen, Chengjun Li, Bin Li","doi":"10.1080/07391102.2024.2306499","DOIUrl":"10.1080/07391102.2024.2306499","url":null,"abstract":"<p><p>Red flour beetle, <i>Tribolium castaneum</i>, has a major negative impact during storage of agricultural products and reveals the negative impacts on human health. Insect-specific epsilon glutathione S-transferase (GSTs) which requires reduced glutathione (GSH) as an essential substrate not only develop insecticide resistance but also play important role in insect metamorphosis. Inhibition of the insect metamorphosis and the development of insecticide resistance could play an important role in pest control, so <i>T. castaneum</i> GSTe2 (TcGSTe2) in our previous study could be an important target protein for this purpose. This study aimed to find a potential TcGSTe2 inhibitors through <i>in silico</i> mothods, including molecular modeling, molecular docking, ADMET assay, followed by molecular dynamics (MD) simulation, principal component analysis and MM/PBSA analysis. The results showed that ZINC000169293362 and ZINC000095566957 were selected as potential TcGSTe2 inhibitors with high-binding affinity and without any toxicity from 3618 of GSH-like compounds obtained from ZINC database. MD simulation results revealed that TcGSTe2-ZINC000169293362 had more stability than that of reference GSH. Moreover, TcGSTe2-ZINC000169293362 and TcGSTe2-ZINC000095566957 showed lower binding free energy (-27.53 ± 0.16 kcal/mol and -18.83 ± 0.15 kcal/mol, respectively) compared with TcGSTe2-GSH (-8.90 ± 0.30 kcal/mol). This study could provide new insight into reduction of insecticide resistance and be used to design new inhibitors of insect GSTs.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5074-5085"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139546527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New thiazolyl-isoxazole derivatives as potential anti-infective agents: design, synthesis, <i>in vitro</i> and <i>in silico</i> antimicrobial efficacy.","authors":"Manish R Bhoye, Abhijit Shinde, Abdul Latif N Shaikh, Vilas Shisode, Abhijit Chavan, Deepika Maliwal, Raghuvir R S Pissurlenkar, Pravin C Mhaske","doi":"10.1080/07391102.2024.2306497","DOIUrl":"10.1080/07391102.2024.2306497","url":null,"abstract":"<p><p>Antimicrobial resistance threatens the efficacious prevention and treatment of infectious diseases caused by microorganisms. To combat microbial infections, the need for new drug candidates is essential. In this context, the design, synthesis, antimicrobial screening, and <i>in silico</i> study of a new series of 5-aryl-3-(2-arylthiazol-4-yl)isoxazole (<b>9a-t</b>) have been reported. The structure of new compounds was confirmed by spectrometric methods. Compounds <b>9a-t</b> were evaluated for <i>in vitro</i> antitubercular and antimicrobial activity. Against <i>M. tuberculosis</i> H37Rv, fourteen compounds showed good to excellent antitubercular activity with MIC 2.01-9.80 µM. Compounds <b>9a</b>, <b>9b,</b> and <b>9r</b> showed four-fold more activity than the reference drug isoniazid. Nine compounds, <b>9a</b>, <b>9b</b>, <b>9d</b>, <b>9e</b>, <b>9i</b>, <b>9q</b>, <b>9r</b>, <b>9s</b>, <b>and 9t,</b> showed good antibacterial activity against <i>E. coli</i> with MIC 7.8-15.62 µg/mL. Against <i>A. niger</i>, four compounds showed good activity with MIC 31.25 µg/mL. Against <i>C. albicans</i>, all twenty compounds reported excellent to good activity with MIC 7.8-31.25 µg/mL. Compounds <b>9c-e</b>, <b>9g-j</b>, and <b>9q-t</b> showed comparable activity concerning the reference drug fluconazole. The compounds <b>9a-t</b> were screened for cytotoxicity against 3t3l1 cell lines and found to be less or non-cytotoxic. The <i>in silico</i> study exposed that these compounds displayed high affinity towards the <i>M. tuberculosis</i> targets PanK, DprE1, DHFR, PknA, KasA, and Pks13, and <i>C. albicans</i> targets NMT, CYP51, and CS. The compound <b>9r</b> was evaluated for structural dynamics and molecular dynamics simulations. The potent antitubercular and antimicrobial activity of 5-aryl-3-(2-arylthiazol-4-yl)isoxazole (<b>9a-t)</b> derivatives has recommended that these compounds could assist in treating microbial infections.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5053-5067"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139521044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational exploration of FOXM1 inhibitors for glioblastoma: an integrated virtual screening and molecular dynamics simulation study.","authors":"Kumari Swati, Sudhir Rama Varma, R P Parameswari, Siva Prasad Panda, Mohit Agrawal, Anand Prakash, Dhruv Kumar, Prasoon Agarwal","doi":"10.1080/07391102.2024.2308772","DOIUrl":"10.1080/07391102.2024.2308772","url":null,"abstract":"<p><p>In this study, a comprehensive investigation of a set of phytochemicals to identify potential inhibitors for the Forkhead box protein M1 (FOXM1) was conducted. FOXM1 is overexpressed in glioblastoma (GBM) cells and plays a crucial role in cell cycle progression, proliferation, and invasion. FOXM1 inhibitors have shown promising results in preclinical studies, and ongoing clinical trials are assessing their efficacy in GBM patients. However, there are limited studies on the identification of novel compounds against this attractive therapeutic target. To address this, the NPACT database containing 1,574 phytochemicals was used, employing a hierarchical multistep docking approach, followed by an estimation of relative binding free energy. By fixing user-defined XP-dock and MM-GBSA cut-off scores of -6.096 and -37.881 kcal/mol, the chemical space was further narrowed. Through exhaustive analysis of molecular binding interactions and various pharmacokinetics profiles, we identified four compounds, namely NPACT00002, NPACT01454, NPACT00856, and NPACT01417, as potential FOXM1 inhibitors. To assess the stability of protein-ligand binding in dynamic conditions, 100 ns Molecular dynamics (MD) simulations studies were performed. Furthermore, Molecular mechanics with generalized Born and surface area solvation (MM-GBSA) based binding free energy estimations of the entire simulation trajectories revealed a strong binding affinity of all identified compounds towards FOXM1, surpassing that of the control drug Troglitazone. Based on extensively studied multistep docking approaches, we propose that these molecules hold promise as FOXM1 inhibitors for potential therapeutic applications in GBM. However, experimental validation will be necessary to confirm their efficacy as targeted therapies.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5199-5217"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A discovery of potent kaempferol derivatives as multi-target medicines against diabetes as well as bacterial infections: an <i>in silico</i> approach.","authors":"Shagufta Parveen, Saman Shehzadi, Nusrat Shafiq, Maryam Rashid, Sadaf Naz, Tahir Mehmood, Rabia Riaz, Khalid S Almaary, Hiba-Allah Nafidi, Mohammed Bourhia","doi":"10.1080/07391102.2024.2308773","DOIUrl":"10.1080/07391102.2024.2308773","url":null,"abstract":"<p><p>Flavonoids demonstrate beneficial effects on human health because flavonoids contain important biological properties. Kaempferol is a flavonol, type of flavonoid found in eatable plants and in plants usually employed in ancient drugs (<i>Moringa oleifera</i>, Tilia spp., fern genus spp. and gingko etc.). Some medicinal studies have shown that the use of foods full of kaempferol decreases the risk of many (cancer, vascular) diseases. All the data of 50 kaempferol derivatives were collected from PubChem database. Through Schrödinger software, 3D-QSAR study was performed for 50 compounds by using method of field base. Conformer of kaempferol derivatives was docked against anti-diabetic, anti-microbial co-crystal structures and protein. To monitor the best anti-diabetic and antibacterial agent, particular kaempferol derivatives were downloaded from PubChem database. Virtual screening by molecular docking provided four lead compounds with four different proteins. These hit compounds were found to be potent inhibitor for diabetic enzymes alpha-amylase and DPP IV and had the potential to suppress DNA gyrase and dihydrofolate reductase synthesis. Molecular dynamic simulation of docked complexes evaluates the value of root mean square fluctuation by iMOD server. Kaempferol 3-O-alpha-L-(2, 3-di-Z-p-coumaroyl) rhamnoside <b>(42)</b> compound used as anti-diabetic and kaempferol 3-O-gentiobioside <b>(3)</b> as antibacterial with good results can be used for drug discovery.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"5218-5240"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139706889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}